Factors associated with improved outcomes for metastatic inflammatory breast cancer patients.

PURPOSE: Controversy exists regarding the role of locoregional therapy for stage IV inflammatory breast cancer (IBC). This study aims to determine indicators of prognosis, including primary tumor resection, for stage IV IBC patients. METHODS: Using the National Cancer Data Base, female patients diagnosed 2010-2013 with unilateral a priori metastatic T4d invasive adenocarcinoma of the breast were identified. We conducted propensity score matched analysis to balance confounders of surgery versus no-surgery. Stratified log-rank test and double-robust estimation under the Cox model were used to assess the effect of surgery, and margins, on overall survival (OS) in the propensity score matched cohort. RESULTS: Of 1266 patients, 41% underwent surgery. In the unmatched cohort, median OS of the surgery and no-surgery groups was 36 and 20 months, respectively (p < 0.001). In the matched cohort (n = 588), the median OS of surgery and no-surgery groups was 29 and 27 months, respectively (p = 0.052). Patients with negative margin surgery (p = 0.024), hormone receptor-positive (p = 0.019), HER2-positive disease (p < 0.0001), treated with chemotherapy (p < 0.0001) and hormonal therapy (p < 0.0001), had better survival. Those with brain metastases had increased risk of death (p < 0.0001). CONCLUSION: This study represents the largest cohort of metastatic IBC patients, and identified negative margin surgery, systemic therapy, hormone receptor and HER2-positive disease as factors associated with improved outcomes. While these findings should be interpreted cautiously, they may be used to guide further investigations into local control and quality of life in this patient population with limited treatment options.

Long-Term Safety of Observation in Selected Women Following Core Biopsy Diagnosis of Atypical Ductal Hyperplasia.

PURPOSE: Atypical ductal hyperplasia (ADH) found on core biopsy is associated with an upgrade to carcinoma in 10-30 % of women, thus surgical excision remains the standard of care. This study compares the incidence of breast cancer in women with ADH who were observed with those who underwent surgical excision of the ADH site. METHODS: Our departmental, prospectively maintained registry was reviewed to identify patients with ADH diagnosed by core biopsy. Surgically treated patients were excluded if upstaged to carcinoma following excision for ADH diagnosis. Breast cancer events were classified as index site (site of ADH biopsy), ipsilateral breast unrelated to index site, or contralateral breast. RESULTS: Overall, 175 women met the study criteria; 125 were observed and 50 underwent excision. With a median follow-up of 3 years, 14 breast cancer events were noted in 13 patients. In the surgery group, six women developed breast cancer (12 %), including one bilateral, compared with seven cancers (5.6 %) in the observed group (p = 0.14). Index site events and ipsilateral cancers were the same in both groups [2 vs. 0.8 % (p = 0.49) and 4 versus 4.8 % (p = 1.00), respectively]. All contralateral cancers occurred in the surgical group (8 vs. 0 %; p < 0.01). A prior history of breast cancer was the only variable associated with subsequent breast cancer events (hazard ratio 12.53, 95 % confidence interval 3.30-47.57). CONCLUSION: Observation is appropriate in selected women with ADH on core biopsy. Index site failures are rare and are superseded by cancer risk elsewhere in the breast.

Considerations for the Treatment of Young Patients with Breast Cancer.

Breast cancer in the young patient, generally defined as younger than 40 years, is a rare but important problem. In the US, over 24,000 women under age 45 are diagnosed with breast cancer each year and nearly 2,500 young women die annually of the disease. This review is intended to address issues specific to caring for the young breast cancer patient including diagnosis, genetic counseling, tumor biology, surgery, and potential for development of contralateral breast cancer. Additionally, there are psychosocial considerations unique to this age group which should be addressed as part of a comprehensive, multi-disciplinary team approach including discussions about fertility, sexual function, behavioral health, and quality of life.

Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer.

BACKGROUND/AIMS: Laparoscopy is important in staging pancreatic cancer, but false negatives remain problematic. Making tumors fluorescent has the potential to improve the accuracy of staging laparoscopy. METHODOLOGY: Orthotopic and carcinomatosis models of pancreatic cancer were established with BxPC-3 human pancreatic cancer cells in nude mice. Alexa488-antiCEA conjugates were injected via tail vein 24 hours prior to laparoscopy. Mice were examined under bright field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes measured included time to identification of primary tumor for the orthotopic model and number of metastases identified within 2 minutes for the carcinomatosis model. RESULTS: FL enabled more rapid and accurate identification and localization of primary tumors and metastases than BL. Using BL took statistically significantly longer time than FL (p<0.0001, fold change and 95% CI for BL vs. FL: 8.12 (4.54,14.52)). More metastatic lesions were detected and localized under FL compared to BL and with greater accuracy, with sensitivities of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough to detect metastatic lesions <1mm. CONCLUSIONS: The use of fluorescence laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody permits rapid detection and accurate localization of primary and metastatic pancreatic cancer in an orthotopic model. The results of the present report demonstrate the future clinical potential of fluorescence laparoscopy.

Treatment of Tracheoinnominate Fistula with Ligation of the Innominate Artery: A Case Report.

INTRODUCTION: Tracheoinnominate fistula, a rare complication of tracheostomy, carries high mortality regardless of treatment; therefore prevention and quick diagnosis is pertinent to survival. CASE PRESENTATION: A 76-year-old man who underwent emergent tracheostomy placement presented on postoperative day 10 with massive hemorrhage concerning for tracheoinnominate fistula and was treated with median sternotomy and ligation of the innominate artery. DISCUSSION: This presentation describes a concise diagnosis and treatment plan for a rare event. The key to good outcomes is quick diagnosis and urgent surgical intervention.

Detection of colon cancer metastases with fluorescence laparoscopy in orthotopic nude mouse models.

OBJECTIVE: To improve detection of colon cancer metastases using fluorescence laparoscopy (FL). DESIGN: An orthotopic mouse model of human colon cancer was established by intracecal injection of HCT-116 human colon cancer cells expressing green fluorescent protein into 12 mice. One group modeled early disease and the second modeled late metastatic disease. For the early-disease model, 2 weeks after implantation, 6 mice underwent 2 modalities of laparoscopy: bright field laparoscopy (BL) and FL. The number of metastases identified within each of the 4 abdominal quadrants was recorded with both laparoscopy modalities. This process was repeated in the late-metastatic disease group 4 weeks after implantation. All animals were then humanely sacrificed and imaged using open fluorescence laparoscopy (OL) as a positive control to identify metastases. SETTING: Basic science laboratory. PARTICIPANTS: Twelve female, 6-week-old nude mice. INTERVENTIONS: Detection of tumor foci by FL compared with BL. MAIN OUTCOME MEASURES: Number of tumors identified in each quadrant. RESULTS Fluorescence laparoscopy enabled superior visualization of colon cancer metastases compared with BL in the early (P = .03) and late (P = .002) models of colon cancer. Compared with OL, BL was significantly inferior in the early (P = .04) and late (P < .001) groups. Fluorescence laparoscopy was not significantly different from OL in the early (P = .85) or late (P = .46) group. Thus, FL allowed identification of micrometastases that could not be distinguished from surrounding tissue using BL. CONCLUSIONS: The use of FL enables identification of metastases that could not be visualized using standard laparoscopy. This report illustrates the important clinical potential for FL in the surgical treatment of cancer.

Tumor-educated macrophages promote tumor growth and peritoneal metastasis in an orthotopic nude mouse model of human pancreatic cancer.

BACKGROUND: Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, intravasation, and suppression of antitumor immune responses. MATERIALS AND METHODS: Ten transgenic nude mice, ubiquitously expressing green fluorescent protein (GFP), were injected subcutaneously with the human pancreatic cancer cell line, BXPC3, stably expressing red fluorescent protein (RFP). GFP-expressing macrophages from the GFP mice with the subcutaneous BxPC3-RFP tumor were harvested and defined as "tumor-educated macrophages". Macrophages were also harvested from transgenic GFP mice (n=10) without tumors and identified as "naïve macrophages." The tumor-educated and naïve macrophages were then implanted into BxPC-3-RFP tumor-bearing non-transgenic nude mice and compared for their ability to enhance tumor progression. RESULTS: In the control group, without macrophage injection, the average primary tumor weighed 668 mg and only three mice (30%) developed peritoneal metastases, which averaged 72 mg. The naïve-macrophage group had an average tumor weight of 823 mg (p=0.51) and 50% developed peritoneal metastases, whose weight averaged 975 mg (p=0.029). The group treated with tumor-educated macrophages had an average primary tumor weight of 2095 mg (p=0.001) and 75% of mice developed peritoneal metastases, whose weight averaged 2135 mg (p=0.008). CONCLUSION: These results suggest that macrophages influence tumors, and tumors influence macrophages, and tumor-educated promote tumor progression. Tumor-educated macrophages may be a target for therapy of metastatic cancer.

A rapid imageable in vivo metastasis assay for circulating tumor cells.

Circulating tumor cells (CTCs) are of great importance for cancer diagnosis, prognosis and treatment. It is necessary to improve the ability to image and analyze them for their biological properties which determine their behavior in the patient. In the present study, using immunomagnetic beads, CTCs were rapidly isolated from the circulation of mice orthotopically implanted with human PC-3 prostate cancer cells stably expressing green fluorescent protein (GFP). The PC-3-GFP CTCs were then expanded in culture in parallel with the parental PC-3-GFP cell line. Both cell types were then inoculated onto the chorioallentoic membrane (CAM) of chick embryos. Eight days later, embryos were harvested and the brains were processed for frozen sections. The IV-100 intravital laser scanning microscope enabled rapid identification of fluorescent metastatic foci within the chick embryonic brain. Inoculation of embryos with PC-3-GFP CTCs resulted in a 3 to 10-fold increase in brain metastasis when compared to those with the parental PC-3-GFP cells (p<0.05 in all animals). Thus, PC-3-GFP CTCs have increased metastatic potential compared to their parental counterparts. Furthermore, the chick embryo represents a rapid, sensitive, imageable assay of metastatic potential for CTCs. The chick embryo assay has future clinical application for individualizing patient therapy based on the metastatic profile of their CTCs.

Submillimeter-resolution fluorescence laparoscopy of pancreatic cancer in a carcinomatosis mouse model visualizes metastases not seen with standard laparoscopy.

BACKGROUND: Staging laparoscopy can visualize peritoneal and liver metastases in pancreatic cancer otherwise undetectable by preoperative imaging. However, false-negative rates may be as high as 18%-26%. The aim of the present study was to improve detection of metastatic pancreatic cancer with the use of fluorescence laparoscopy (FL) in a nude-mouse model with the tumors expressing green fluorescent protein (GFP). METHODS: The carcinomatosis mouse model of human pancreatic cancer was established by intraperitoneal injections of green fluorescent protein-expressing MiaPaca-2 human pancreatic cancer cells into 6-week-old female athymic mice. Two weeks later, mice underwent diagnostic laparoscopy. Laparoscopy was performed first under standard brightfield lighting, followed by fluorescent lighting. The number of metastatic foci identified within the four quadrants of the peritoneal cavity was recorded. After laparoscopy, the animals were sacrificed, opened, and imaged with the OV-100 Small Animal Imaging system as a positive control to identify metastasis. Tumors were collected and processed for histologic review. RESULTS: FL enabled visualization of pancreatic cancer metastatic foci not visualized with standard brightfield laparoscopy (BL). Under FL, in 1 representative mouse, 26 separate micrometastatic lesions were identified. In contrast, only very large tumors were seen using BL. Use of the OV-100 images, as positive controls, confirmed the presence of tumor foci. FL thus allowed identification and exact localization of submillimeter tumor foci. Such small-sized tumor foci were not distinguished from surrounding tissue under BL. All malignant lesions were histologically confirmed. CONCLUSIONS: The use of FL enables the identification of tumor foci that cannot be seen with standard laparoscopy. The technology described in this report has important potential for the clinical development of FL.